Research Training and Scholarly Activity during General Pediatric Residency in Canada.

OBJECTIVE: To describe the characteristics of research training and scholarly activity during pediatrics residency in Canada and identify facilitators and barriers to resident scholarly activity. STUDY DESIGN: We conducted a mixed-methods, cross-sectional survey of pediatrics residents in Canada from April to June 2023. Trainees and medical education experts developed the 55-item survey, pilot tested, and distributed electronically to residents in all 17 Canadian residency programs. Responses were complemented with program-level data from pediatrics residency program directors. RESULTS: Of 644 Canadian pediatrics residents, 230 (36%) responded. Resident respondents conducted various types of scholarly projects, including retrospective clinical study (22%), qualitative research (15%), quality improvement (13%), and medical education research (12%). Discordance between the field of career interests and primary scholarly projects was common. Among respondents, 20% had abstracts accepted at national or international conferences, and 12% had manuscripts submitted to peer-reviewed journals. Resident respondents' self-perceived progress in their scholarly projects were discrepant from their actual progress. Key themes related to barriers and facilitators to scholarly activity included protected time for research, mentorship, and research skills training. CONCLUSIONS: The research training and scholarly activity of pediatrics residents in Canada is variable. Establishing national standards, implementing progress monitoring mechanisms with tailored support, and offering flexible protected research time are important next steps.

Give me a break! Addressing observed structured clinical exam anxiety.

WHAT WAS THE EDUCATIONAL CHALLENGE?: Medical students experience high rates of anxiety; frequent examinations are one contributing source. Students may perceive the observed structured clinical examinations (OSCEs) as particularly stressful. Strategies to reduce anxiety during OSCEs have not been described. WHAT WAS THE SOLUTION?: We sought to implement and evaluate a simple, in-the-moment intervention aimed at reducing students' OSCE-related anxiety by making stress-reducing activities available during break stations during a summative pediatric OSCE. HOW WAS THE SOLUTION IMPLEMENTED?: Three break stations were included in an end-of-rotation, summative OSCE. Students were block-randomized to either control group with standard break stations, or intervention group with stress-reducing activities available in the break room. All participants completed the State-Trait Anxiety Inventory (STAI) before and after the OSCE, and a short questionnaire after OSCE completion. WHAT LESSONS WERE LEARNED THAT ARE RELEVANT TO A WIDER GLOBAL AUDIENCE?: Third-year medical students have high levels of stress before and after OSCEs. More than half of students in the intervention group felt their anxiety improved with activities. While the inclusion of stress-reducing activities in break stations did not impact exam performance, some students subjectively felt their performance improved. If OSCE break stations are logistically required, they can be employed to allow students to briefly relax during a high-stress exam without negatively impacting performance. WHAT ARE THE NEXT STEPS?: Next steps include exploration of opportunities for integration of stress-reducing activities during OSCEs with other learner groups, and identification of other stress-inducing aspects of medical training to provide similar opportunities.

Extracellular vesicles as markers and mediators of pregnancy complications: gestational diabetes, pre-eclampsia, preterm birth and fetal growth restriction.

In high income countries, approximately 10% of pregnancies are complicated by pre-eclampsia (PE), preterm birth (PTB), fetal growth restriction (FGR) and/or macrosomia resulting from gestational diabetes (GDM). Despite the burden of disease this places on pregnant people and their newborns, there are still few, if any, effective ways of preventing or treating these conditions. There are also gaps in our understanding of the underlying pathophysiologies and our ability to predict which mothers will be affected. The placenta plays a crucial role in pregnancy, and alterations in placental structure and function have been implicated in all of these conditions. As extracellular vesicles (EVs) have emerged as important molecules in cell-to-cell communication in health and disease, recent research involving maternal- and placental-derived EV has demonstrated their potential as predictive and diagnostic biomarkers of obstetric disorders.  This review will consider how placental and maternal EVs have been investigated in pregnancies complicated by PE, PTB, FGR and GDM and aims to highlight areas where further research is required to enhance the management and eventual treatment of these pathologies.

Inequity in end-of-life care for patients with chronic liver disease in England.

BACKGROUND AND AIMS: The World Health Assembly recommends integration of palliative care into treatment of patients with any life-limiting condition, yet patients with non-malignant disease are less likely to receive specialist palliative care (SPC). This study compares SPC offered to patients with hepatocellular carcinoma (HCC) versus patients with chronic liver disease without HCC (CLD without HCC). METHODS: Patients who died from CLD or HCC over 5 years (2013-2017) in England were identified using a dataset linking national data on all hospital admissions (Hospital Episode Statistics - HES) with national mortality data from the Office for National Statistics (HES - ONS). The primary outcome was the proportion of patients who received inpatient SPC in their last year of life (LYOL). Secondary outcomes were (1) early inpatient SPC input and (2) the proportion dying in a hospice. The outcomes were compared between patients with HCC and CLD without HCC. RESULTS: 29 669 patients were identified, 8143 of whom had HCC. Patients with HCC were significantly more likely to receive inpatient SPC input-adjusted OR 3.74 (95% CI 3.52-3.97) and early inpatient SPC input-adjusted OR 7.26 (95% CI 6.38-8.25) and die in a hospice OR 8.23 (95% CI 7.33-9.24) than patients with CLD without HCC. CONCLUSIONS: These data highlight the stark inequity in access to SPC services between patients with HCC and patients with CLD without HCC in England. Addressing these inequities will improve end-of-life care for patients with CLD.

Disseminating evidence in medical education: journal club as a virtual community of practice.

BACKGROUND: This study explores the impacts of the Council on Medical Student Education in Pediatrics (COMSEP) Journal Club, a unique means of providing monthly professional development for a large international community of pediatric undergraduate medical educators. In particular, we sought to establish member engagement with the Journal Club, identify factors impacting member contributions to the Journal Club, and determine perceived benefits of and barriers to participation as a Journal Club reviewer. METHODS: Using an established Annual Survey as a study instrument, six survey questions were distributed to members of COMSEP. Items were pilot tested prior to inclusion. Quantitative data were analyzed using descriptive statistics and chi-square analysis.. RESULTS: Of 125 respondents who completed the survey, 38% reported reading the Journal Club most months or always. Level of engagement varied. Reasons for reading included a topic of interest, keeping up to date on medical education literature, gaining practical tips for teaching and implementing new curricula. Motivators for writing a review included keeping up to date, contributing to a professional organization, and developing skill in analyzing medical education literature, with a minority citing reasons of enhancing their educational portfolio or academic promotion. The most commonly cited barriers were lack of time and lack of confidence or training in ability to analyze medical education literature. CONCLUSION: As a strategy to disseminate the latest evidence in medical education to its membership, the COMSEP Journal Club is effective. Its format is ideally suited for busy educators and may help in members' professional development and in the development of a community of practice.

Placental expression of estrogen-related receptor gamma is reduced in fetal growth restriction pregnancies and is mediated by hypoxia†.

Fetal growth restriction (FGR) describes a fetus which has not achieved its genetic growth potential; it is closely linked to placental dysfunction and uteroplacental hypoxia. Estrogen-related receptor gamma (ESRRG) is regulated by hypoxia and is highly expressed in the placenta. We hypothesized ESRRG is a regulator of hypoxia-mediated placental dysfunction in FGR pregnancies. Placentas were collected from women delivering appropriate for gestational age (AGA; n = 14) or FGR (n = 14) infants. Placental explants (n = 15) from uncomplicated pregnancies were cultured for up to 4 days in 21% or 1% O2, or with 200 µM cobalt chloride (CoCl2), or treated with the ESRRG agonists DY131 under different oxygen concentrations. RT-PCR, Western blotting, and immunochemistry were used to assess mRNA and protein levels of ESRRG and its localization in placental tissue from FGR or AGA pregnancies, and in cultured placental explants. ESRRG mRNA and protein expression were significantly reduced in FGR placentas, as was mRNA expression of the downstream targets of ESRRG, hydroxysteroid 11-beta dehydrogenase 2 (HSD11B2), and cytochrome P-450 (CYP19A1.1). Hypoxia-inducible factor 1-alpha protein localized to the nuclei of the cytotrophoblasts and stromal cells in the explants exposed to CoCl2 or 1% O2. Both hypoxia and CoCl2 treatment decreased ESRRG and its downstream genes' mRNA expression, but not ESRRG protein expression. DY131 increased the expression of ESRRG signaling pathways and prevented abnormal cell turnover induced by hypoxia. These data show that placental ESRRG is hypoxia-sensitive and altered ESRRG-mediated signaling may contribute to hypoxia-induced placental dysfunction in FGR. Furthermore, DY131 could be used as a novel therapeutic approach for the treatment of placental dysfunction.

Sex-specific effects of bisphenol A on the signaling pathway of ESRRG in the human placenta†.

Bisphenol A (BPA) exposure during pregnancy is associated with low fetal weight, particularly in male fetuses. The expression of estrogen-related receptor gamma (ESRRG), a receptor for BPA in the human placenta, is reduced in fetal growth restriction. This study sought to explore whether ESRRG signaling mediates BPA-induced placental dysfunction and determine whether changes in the ESRRG signaling pathway are sex-specific. Placental villous explants from 18 normal term pregnancies were cultured with a range of BPA concentrations (1 nM-1 µM). Baseline BPA concentrations in the placental tissue used for explant culture ranged from 0.04 to 5.1 nM (average 2.3 ±1.9 nM; n = 6). Expression of ESRRG signaling pathway constituents and cell turnover were quantified. BPA (1 µM) increased ESRRG mRNA expression after 24 h in both sexes. ESRRG mRNA and protein expression was increased in female placentas treated with 1 µM BPA for 24 h but was decreased in male placentas treated with 1 nM or 1 µM for 48 h. Levels of 17ß-hydroxysteroid dehydrogenase type 1 (HSD17B1) and placenta specific-1 (PLAC1), genes downstream of ESRRG, were also affected. HSD17B1 mRNA expression was increased in female placentas by 1 µM BPA; however, 1 nM BPA reduced HSD17B1 and PLAC1 expression in male placentas at 48 h. BPA treatment did not affect rates of proliferation, apoptosis, or syncytiotrophoblast differentiation in cultured villous explants. This study has demonstrated that BPA affects the ESRRG signaling pathway in a sex-specific manner in human placentas and a possible biological mechanism to explain the differential effects of BPA exposure on male and female fetuses observed in epidemiological studies.

IL-35-mediated induction of a potent regulatory T cell population.

Regulatory T cells (T(reg) cells) have a critical role in the maintenance of immunological self-tolerance. Here we show that treatment of naive human or mouse T cells with IL-35 induced a regulatory population, which we call 'iT(R)35 cells', that mediated suppression via IL-35 but not via the inhibitory cytokines IL-10 or transforming growth factor-ß (TGF-ß). We found that iT(R)35 cells did not express or require the transcription factor Foxp3, and were strongly suppressive and stable in vivo. T(reg) cells induced the generation of iT(R)35 cells in an IL-35- and IL-10-dependent manner in vitro and induced their generation in vivo under inflammatory conditions in intestines infected with Trichuris muris and within the tumor microenvironment (B16 melanoma and MC38 colorectal adenocarcinoma), where they contributed to the regulatory milieu. Thus, iT(R)35 cells constitute a key mediator of infectious tolerance and contribute to T(reg) cell-mediated tumor progression. Furthermore, iT(R)35 cells generated ex vivo might have therapeutic utility.

Embracing uncertainty: medical student perceptions of a pediatric bootcamp developed in response to mandated changes during the pandemic.

BACKGROUND: The start of the COVID-19 pandemic led to both shortened clinical rotations and consequent loss of embedded formal teaching time. In response to these learning gaps, a novel, virtual pediatric bootcamp was developed to provide a consolidated 3-week learning opportunity for clinical medical students. Pre-clinical students were encouraged but not required to participate, given the suspension of clinical patient experiences for all undergraduate medical learners and the uncertainty of when clinical rotations would resume. This group of students were particularly challenged with adapting their learning in response to the pandemic while also preparing to apply their pre-clinical knowledge to solve clinical problems. METHODS: A qualitative thematic analysis was used for this study. Ten semi-structured phone interviews were conducted with second-year medical students to explore their experiences and perceptions of the pediatric bootcamp. The six phases of thematic analysis proposed by Braun and Clark guided data analysis. To ensure rigour, the three aspects of rigour-credibility, transferability and confirmability were utilized throughout the project. RESULTS: Qualitative exploration from semi-structured phone interviews of second-year medical students' perceptions and experiences of this new and unanticipated learning experience revealed four main themes: (a) clinical relevance, describing how students were pushed to think about clinical problems in a new way; (b) timing, which explored conflicts related to competing interests, mental preparedness, and the interval between learning and application; (c) teaching strategies, describing how active learning and interaction were facilitated and challenges that arose; and (d) learning resources, highlighting the curated and accessible resources made available to the students, as well as those resources that learners develop for themselves. CONCLUSIONS: A novel three-week online case-based pediatric bootcamp fostered application of knowledge for clinical reasoning at a time when students were transitioning from preclinical to clinical learning. Students were stretched to balance competing priorities, and the bootcamp curated synchronous and asynchronous learner opportunities while allowing them to reflect on their own learning styles and effective virtual learning strategies. While bootcamps are often used to prepare learners for transitions between clinical stages, our findings suggest the bootcamp format can also facilitate transition from preclinical to clinical roles.

From vision to implementation: Building a national undergraduate paediatric curriculum.

Objective: There are many challenges in ensuring medical students learn paediatrics. Medical educators must develop and maintain curricula that meet learners' needs and accreditation requirements. Paediatricians and family physicians, practicing and teaching in busy clinical environments, require Canadian-relevant curricular guidance and resources to teach and assess learners. Students struggle with curricular cohesion, clear expectations, and resources. Recognizing these challenges and acknowledging the need to address them, the Paediatric Undergraduate Program Directors of Canada (PUPDOC) created canuc-paeds, a comprehensive competency-based undergraduate curriculum that teachers and students would actually use. Methods: Curriculum development included the following: utilization of best practices in curriculum development, an environmental scan, development of guiding principles, Delphi surveys, in-person meetings, and quality improvement. All Canadian paediatric undergraduate educator leaders and other stakeholders were invited to participate. Results: The curriculum, based on the RCPSC CanMEDS Framework, includes 29 clinical presentations, each with key conditions, foundational knowledge objectives, and learning resources. Essential paediatric-specific physical examination and procedural skills that graduating medical students are expected to perform are identified. Objectives specific to Intrinsic Roles of Collaborator, Communicator, Professional, Leader, Health Advocate and Scholar that can be assessed in the field of paediatrics at the undergraduate level are articulated. The national curriculum has been implemented widely at Canadian medical schools. Online, open-access clinical resources have been developed and are being used world-wide. Conclusion: This curriculum provides overarching Canadian-specific curricular guidance and resources for students and for the paediatricians and family physicians who are responsible for teaching and assessing undergraduate learners.

The potential role of the E SRRG pathway in placental dysfunction.

Normal placental development and function is of key importance to fetal growth. Conversely aberrations of placental structure and function are evident in pregnancy complications including fetal growth restriction (FGR) and preeclampsia. Although trophoblast turnover and function is altered in these conditions, their underlying aetiologies and pathophysiology remains unclear, which hampers development of therapeutic interventions. Here we review evidence that supports a role for estrogen related receptor-gamma (ESRRG) in the development of placental dysfunction in FGR and preeclampsia. This relationship deserves particular consideration because ESRRG is highly expressed in normal placenta, is reduced in FGR and preeclampsia and its expression is altered by hypoxia, which is thought to result from deficient placentation seen in FGR and preeclampsia. Several studies have also found microRNA (miRNA) or other potential upstream regulators of ESRRG negatively influence trophoblast function which could contribute to placental dysfunction seen in FGR and preeclampsia. Interestingly, miRNAs regulate ESRRG expression in human trophoblast. Thus, if ESRRG is pivotally associated with the abnormal trophoblast turnover and function it may be targeted by microRNAs or other possible upstream regulators in the placenta. This review explores altered expression of ESRRG and upstream regulation of ESRRG-mediated pathways resulting in the trophoblast turnover, placental vascularisation, and placental metabolism underlying placental dysfunctions. This demonstrates that the ESRRG pathway merits further investigation as a potential therapeutic target in FGR and preeclampsia.

Interaction between Metformin, Folate and Vitamin B12 and the Potential Impact on Fetal Growth and Long-Term Metabolic Health in Diabetic Pregnancies.

Metformin is the first-line treatment for many people with type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) to maintain glycaemic control. Recent evidence suggests metformin can cross the placenta during pregnancy, thereby exposing the fetus to high concentrations of metformin and potentially restricting placental and fetal growth. Offspring exposed to metformin during gestation are at increased risk of being born small for gestational age (SGA) and show signs of 'catch up' growth and obesity during childhood which increases their risk of future cardiometabolic diseases. The mechanisms by which metformin impacts on the fetal growth and long-term health of the offspring remain to be established. Metformin is associated with maternal vitamin B12 deficiency and antifolate like activity. Vitamin B12 and folate balance is vital for one carbon metabolism, which is essential for DNA methylation and purine/pyrimidine synthesis of nucleic acids. Folate:vitamin B12 imbalance induced by metformin may lead to genomic instability and aberrant gene expression, thus promoting fetal programming. Mitochondrial aerobic respiration may also be affected, thereby inhibiting placental and fetal growth, and suppressing mammalian target of rapamycin (mTOR) activity for cellular nutrient transport. Vitamin supplementation, before or during metformin treatment in pregnancy, could be a promising strategy to improve maternal vitamin B12 and folate levels and reduce the incidence of SGA births and childhood obesity. Heterogeneous diagnostic and screening criteria for GDM and the transient nature of nutrient biomarkers have led to inconsistencies in clinical study designs to investigate the effects of metformin on folate:vitamin B12 balance and child development. As rates of diabetes in pregnancy continue to escalate, more women are likely to be prescribed metformin; thus, it is of paramount importance to improve our understanding of metformin's transgenerational effects to develop prophylactic strategies for the prevention of adverse fetal outcomes.

Scalable signaling mediated by T cell antigen receptor-CD3 ITAMs ensures effective negative selection and prevents autoimmunity.

The T cell antigen receptor (TCR)-CD3 complex is unique in having ten cytoplasmic immunoreceptor tyrosine-based activation motifs (ITAMs). The physiological importance of this high TCR ITAM number is unclear. Here we generated 25 groups of mice expressing various combinations of wild-type and mutant ITAMs in TCR-CD3 complexes. Mice with fewer than seven wild-type CD3 ITAMs developed a lethal, multiorgan autoimmune disease caused by a breakdown in central rather than peripheral tolerance. Although there was a linear correlation between the number of wild-type CD3 ITAMs and T cell proliferation, cytokine production was unaffected by ITAM number. Thus, high ITAM number provides scalable signaling that can modulate proliferation yet ensure effective negative selection and prevention of autoimmunity.

The paediatrician as a leader: A resident educational intervention for high-value care.

The American College of Physicians defines high-value care (HVC) as health care that balances clinical benefit with costs and harms with the goal of improving patient outcomes. We present a novel 2-hour workshop developed for general paediatric residents designed to promote reflective practice on resource stewardship and raise awareness of costs of medical care in hospitalized children. The workshop impact was assessed quantitatively and qualitatively. Preworkshop, 2-week postworkshop, and 6-month postworkshop electronic surveys were completed by 18 of 43 workshop participants (42% survey participation rate, 100% follow-up in postworkshop surveys) revealing increased knowledge and retention. Thematic analysis performed on 'lessons learned' and 'action plans' provided by participants at the end of the workshop yielded rich data with key findings from learners that included critical thinking about their management and reflecting on nonmonetary costs. Future directions include faculty development and assessment of impact on patient care.

Early specialist palliative care on quality of life for malignant pleural mesothelioma: a randomised controlled trial.

PURPOSE: Malignant pleural mesothelioma (MPM) has a high symptom burden and poor survival. Evidence from other cancer types suggests some benefit in health-related quality of life (HRQoL) with early specialist palliative care (SPC) integrated with oncological services, but the certainty of evidence is low. METHODS: We performed a multicentre, randomised, parallel group controlled trial comparing early referral to SPC versus standard care across 19 hospital sites in the UK and one large site in Western Australia. Participants had newly diagnosed MPM; main carers were additionally recruited. INTERVENTION: review by SPC within 3 weeks of allocation and every 4 weeks throughout the study. HRQoL was assessed at baseline and every 4 weeks with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30. PRIMARY OUTCOME: change in EORTC C30 Global Health Status 12 weeks after randomisation. RESULTS: Between April 2014 and October 2016, 174 participants were randomised. There was no significant between group difference in HRQoL score at 12 weeks (mean difference 1.8 (95% CI -4.9 to 8.5; p=0.59)). HRQoL did not differ at 24 weeks (mean difference -2.0 (95% CI -8.6 to 4.6; p=0.54)). There was no difference in depression/anxiety scores at 12 weeks or 24 weeks. In carers, there was no difference in HRQoL or mood at 12 weeks or 24 weeks, although there was a consistent preference for care, favouring the intervention arm. CONCLUSION: There is no role for routine referral to SPC soon after diagnosis of MPM for patients who are cared for in centres with good access to SPC when required. TRIAL REGISTRATION NUMBER: ISRCTN18955704.

Medical Student Perceptions of On-Call Modalities: A Focus Group Study.

Phenomenon: The call component of clerkship presents students with unique opportunities and challenges. Clerkship programs employ various call modalities, including traditional call, night float, and evening call. The impact of these call models on the student experience has not been explored in depth. Approach: Focus groups were conducted with 4th-year medical students, exploring their multidimensional experiences with various call modalities during clerkship. Transcripts were analyzed using thematic analysis. Findings: Thirty-nine students participated in 6 focus groups. Four overarching themes were identified: (a) educational value conferred by clinical exposure and teaching, (b) maintaining quality of life and developing features of burnout, (c) formation of professional identity via relationships with team members, and (d) perceived quality of patient care provided. Students associated evening call with burnout and poor educational value but also better patient continuity of care. Night float and traditional call contributed to a sense of team bonding and had enhanced perceived educational value while on call but resulted in loss of formal academic teaching time. Insights: Call modality impacts student learning, well-being, professional identity formation, and patient care; however, trade-off among these elements exists across all call models. Enhancing the value of student call experience may be achieved by implementation of various purposeful changes. These may include creating consistency between student and resident call schedules, maximizing recovery time between call shifts, and avoiding scheduling of students for call prior to academic sessions.

Macrophage Exosomes Induce Placental Inflammatory Cytokines: A Novel Mode of Maternal-Placental Messaging.

During pregnancy, the placenta forms the interface between mother and fetus. Highly controlled regulation of trans-placental trafficking is therefore essential for the healthy development of the growing fetus. Extracellular vesicle-mediated transfer of protein and nucleic acids from the human placenta into the maternal circulation is well documented; the possibility that this trafficking is bi-directional has not yet been explored but could affect placental function and impact on the fetus.We hypothesized that the ability of the placenta to respond to maternal inflammatory signals is mediated by the interaction of maternal immune cell exosomes with placental trophoblast. Utilizing the BeWo cell line and whole placental explants, we demonstrated that the human placenta internalizes macrophage-derived exosomes in a time- and dose-dependent manner. This uptake was via clathrin-dependent endocytosis. Furthermore, macrophage exosomes induced release of proinflammatory cytokines by the placenta. Taken together, our data demonstrates that exosomes are actively transported into the human placenta and that exosomes from activated immune cells modulate placental cytokine production. This represents a novel mechanism by which immune cells can signal to the placental unit, potentially facilitating responses to maternal inflammation and infection, and thereby preventing harm to the fetus.

The incompatibility of healthcare services and end-of-life needs in advanced liver disease: A qualitative interview study of patients and bereaved carers.

BACKGROUND: Liver disease represents the third commonest cause of death in adults of working age and is associated with an extensive illness burden towards the end of life. Despite this, patients rarely receive palliative care and are unlikely to be involved in advance care planning discussions. Evidence addressing how existing services meet end-of-life needs, and exploring attitudes of patients and carers towards palliative care, is lacking. AIM: To explore the needs of patients and carers with liver disease towards the end of life, evaluate how existing services meet need, and examine patient and carer attitudes towards palliative care. DESIGN: Qualitative study - semi-structured interviews analysed using thematic analysis. Settings/participants: A total of 17 participants (12 patients, 5 bereaved carers) recruited from University Hospitals Bristol. RESULTS: Participants described escalating physical, psychological and social needs as liver disease progressed, including disabling symptoms, emotional distress and uncertainty, addiction, financial hardship and social isolation. End-of-life needs were incompatible with the healthcare services available to address them; these were heavily centred in secondary care, focussed on disease modification at the expense of symptom control and provided limited support after curative options were exhausted. Attitudes towards palliative care were mixed, however, participants valued opportunities to express future care preferences (particularly relating to avoidance of hospital admission towards the end of life) and an increased focus on symptomatic and logistical aspects of care. CONCLUSION: The needs of patients with liver disease and their carers are frequently incompatible with the healthcare services available to them towards the end of life. Novel strategies, which recognise the life-limiting nature of liver disease explicitly and improve coordination with community services, are required if end-of-life care is to improve.